coagulation

Question 1

what is coagulation?

Answer 1

• process by which blood changes from a liquid into a blood clot
• causes the cessation of blood from a blood vessel

Question 2

what does the coagulation process involve?

Answer 2

• activation
• adhesion
• aggregation of platelets
• deposition of fibrin

Question 3

what can coagulation be divided into?

Answer 3

• primary haemostasis: formation of a platelet plus

- secondary haemostasis: activation of clotting cascade, results in production of fibrin to strengthen platelet plug

Question 4

what are the 3 separate stages to haemostasis?

Answer 4

• vascular phase
• platelet phase
• coagulation phase

Question 5

what happens in the vascular phase?

Answer 5

• damage to blood vessel wall will cause contraction in that area
• occurs due to damage to endothelial cells
• damage causes them to release various factors

Question 6

what are the various factors that are released?

Answer 6

• ADP
• TF (factor 3): need for activation of thrombin from prothrombin
• prostacyclin
• endothelins: stimulate SM contraction, stimulate cell division of endothelial cells, SM cells and fibroblasts –> aid repair of damaged site

Question 7

what also happens to endothelial cells in this phase?

Answer 7

• become sticky
• express surface proteins
• these allow them to stick to other endothelial cells
• attempt to close damaged area

Question 8

what do platelets contain?

Answer 8

• actin and myosin (able to contract)
• no nucleus
• large ER and golgi apparatus for storage of Ca ions
• plenty of mitochondria for ATP formation

Question 9

what do platelets produce?

Answer 9

• prostaglandins
• fibrin-stabilising factor
• PDGF (helps vascular repair)
• thromboxane A2 (prominent vasoconstrictor)

Question 10

describe the membrane of platelets

Answer 10

• special glycoprotein membrane
• prevents adhesion to normal epithelium
• promotes adhesion to damaged epithelium
• particularly adherent to collagen

Question 11

what is a low platelet count called? what causes it?

Answer 11

thrombocytopaenia

• high platelet destruction
• low platelet production

Question 12

what is a high platelet count called? what causes it?

Answer 12

thrombocytosis

• inc. platelet formation
• seen in response to infection, inflammation, cancer

Question 13

what is platelet formation controlled by?

Answer 13

TPO (thrombopoietin) made in liver

Question 14

when does the platelet phase begin?

Answer 14

as soon as platelets begin to attach themselves to damaged areas of endothelium

Question 15

when a platelet becomes attached to a damaged endothelial surface, what happens?

Answer 15

• changes its own shape and size
• will swell
• become large and irregular
• contractile proteins contract causing the release of granules
• ADP, thromboxane, Ca ions released

Question 16

what are the 2 types of granule released by platelets?

Answer 16

• alpha: contain GF e.g. fibrinogen and PDGF

- dense: contain non-protein things e.g. thromboxnae, serotonin, adrenaline, histamine, Ca, ATP

Question 17

what is fibrin? what produces it?

Answer 17

• activated form of fibrinogen
• produced by liver/ platelets
• activated in clotting and forms lots of fibrin threads
• activated fibrin will entangle fibrin and put RBCs into ball

Question 18

what are the 2 separate clotting pathways?

Answer 18

• intrinsic pathway
• extrinisc pathway
• eventually join to form common pathway

Question 19

describe the intrinsic pathway

Answer 19

• begins in blood stream
• activated when blood is exposed to collagen
• F12 is activated by exposed collagen
• F12a activates F11
• F11a combines with Ca and activated F9
• at same time, platelets release PF3 and F8 is activated
• F9a and F8a form F10 activating factor (tenase)

Question 20

describe the extrinsic pathway

Answer 20

• begins in vessel wall
• damaged endothelial cells release F3 (tissue factor)
• TF combines with Ca and activates F7
• F7a-TF complex quickly inactivated by antithrombin III

Question 21

describe the first part of the common pathway, where thrombin gets activated

Answer 21

• F10 is activated by F7a or tenase
• forms F10a (prothrombinase)
• F10a with Ca ions and 5a convert prothrombin into thrombin
• thrombin = F2a

Question 22

what is the relevance of F5 in this step?

Answer 22

not required for this step but when present inc. rate

Question 23

what does thrombin then do?

Answer 23

• activate fibrinogen to firbin
• fibrin strands join together
• with help of F13a it causes cross-linking of fibrin strands

Question 24

what is F13 activated by? what is it also known as?

Answer 24

• activated by thrombin

- fibrin stabilising factor

Question 25

what is the difference in pathways with the levels of thrombin?

Answer 25

• extrinsic produces thrombin v. quickly but in small amounts
• intrinsic pathway produces large amount of thrombin, takes a while to get going

Question 26

What is tissue factor pathway inhibitor?

Answer 26

• directly inhibits F10a

- important in regulating clotting cascade

Question 27

what is antithrombin-III?

Answer 27

enzymes found circulating in blood that binds to thrombin, prevents its action

Question 28

what does activated fibrin do to thrombin?

Answer 28

• will remove and inactivate thrombin

- 90% thrombin produced inactivated in this way